Logic-gated CARs: a unified framework for programmable cell-based delivery systems

Logic-gated chimeric antigen receptors (CARs) enable engineered immune cells to integrate multiple molecular and environmental inputs, improving therapeutic precision, safety, and resistance to antigen escape. As diverse logic-gated CAR architectures have emerged, differences in design principles and terminology have complicated comparisons across studies. This review presents a unified framework for classifying logic-gated CARs according to Boolean logic and biological signal integration, encompassing YES, OR, AND, INHIBIT (AND-NOT), sequential AND-YES/NOT, and hybrid architectures. We compare these systems based on computational logic, molecular mechanisms, reversibility, modularity, and clinical translatability and summarize the evolving clinical landscape of programmable immune cell therapies. This framework provides a practical reference for interpreting, designing, and translating next-generation logic-gated CAR systems.